17-17713995-C-T

Variant names:

• chr17-17713995-C-T
• rs11654526
• NM_030665.4:c.-148-10033C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030665.4(RAI1):​c.-148-10033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,960 control chromosomes in the GnomAD database, including 3,507 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3507 hom., cov: 31)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 8 publications found

Genes affected

RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

RAI1 Gene-Disease associations (from GenCC):

• Smith-Magenis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

LOC124903943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-148-10033C>T		intron_variant	Intron 1 of 5	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-148-10033C>T		intron_variant	Intron 1 of 5	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-148-10033C>T		intron_variant	Intron 2 of 3	3		ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31198 AN: 151842 Hom.: 3500 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31235 AN: 151960 Hom.: 3507 Cov.: 31 AF XY: 0.206 AC XY: 15330 AN XY: 74266

African (AFR) AF: 0.282 AC: 11675 AN: 41426

American (AMR) AF: 0.209 AC: 3188 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1762 AN: 5140

South Asian (SAS) AF: 0.148 AC: 712 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1732 AN: 10560

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11167 AN: 67956

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.179 Hom.: 10881

Bravo AF: 0.217

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11654526; hg19: chr17-17617309;